Review of Published Meta-AnalysesSystematic Review with Evidence Tables

Description of the Methods Used to Analyze the Evidence

Beginning in 2008, Centers for Disease Control and Prevention (CDC) staff members and public- and private-sector experts knowledgeable in the field of sexually transmitted diseases (STDs) systematically reviewed literature using an evidence-based approach (e.g., published abstracts and peer-reviewed journal articles), focusing on the common STDs and information that had become available since publication of the 2006 Guidelines for Treatment of Sexually Transmitted Diseases. CDC staff members and STD experts developed background papers and tables of evidence that summarized the type of study (e.g., randomized controlled trial or case series), study population and setting, treatments or other interventions, outcome measures assessed, reported findings, and weaknesses and biases in study design and analysis. CDC staff then developed a draft document on the basis of this evidence-based review.

Methods Used to Formulate the Recommendations

Expert Consensus (Consensus Development Conference)

Description of Methods Used to Formulate the Recommendations

Centers for Disease Control and Prevention (CDC) staff members and invited consultants (including public- and private-sector professionals knowledgeable in the treatment of patients with sexually transmitted diseases [STDs]) assembled in Atlanta, Georgia, in April 2009 for a meeting where all evidence from the literature reviews pertaining to STD management was discussed.

Specifically, participants identified key questions regarding STD treatment that emerged from the literature reviews and discussed the information available to answer those questions. Discussion focused on four principal outcomes of STD therapy for each individual disease: 1) treatment of infection based on microbiologic eradication, 2) alleviation of signs and symptoms 3) prevention of sequelae, and 4) prevention of transmission. Cost-effectiveness and other advantages (e.g., single-dose formulations and directly observed therapy [DOT]) of specific regimens also were discussed. The consultants then assessed whether the questions identified were relevant, ranked them in order of priority, and answered the questions using the available evidence. In addition, the consultants evaluated the quality of evidence supporting the answers on the basis of the number, type, and quality of the studies.

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Recommendations

Major Recommendations

Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States; an estimated 3.2 million persons are chronically infected. Although HCV is not efficiently transmitted sexually, persons at risk for infection through injection-drug use might seek care in sexually transmitted disease (STD) treatment facilities, human immunodeficiency virus (HIV) counseling and testing facilities, correctional facilities, drug treatment facilities, and other public health settings where STD and HIV prevention and control services are available.

Persons newly infected with HCV typically are either asymptomatic or have a mild clinical illness. HCV ribonucleic acid (RNA) can be detected in blood within 1-3 weeks after exposure. The average time from exposure to antibody to HCV (anti-HCV) seroconversion is 8-9 weeks, and anti-HCV can be detected in >97% of persons by 6 months after exposure. Chronic HCV infection develops in 70%-85% of HCV-infected persons; 60%-70% of chronically infected persons develop evidence of active liver disease. Most infected persons remain unaware of their infection because they are not clinically ill. However, infected persons serve as a source of transmission to others and are at risk for chronic liver disease (CLD) or other HCV-related chronic diseases for decades after infection.

HCV is transmitted through parenteral exposures to contaminated blood, usually through use of injection drugs (sharing of needles or works) and to a lesser extent through exposures in health-care settings as a consequence of inadequate infection-control practices. Transmission rarely follows receipt of blood, tissues, and organs from HCV-infected donors who were not identified during routine screening activities, which have been mandated in the United States since 1992. Occupational and perinatal exposures, although less efficient, also can result in transmission of HCV.

Sexual transmission of HCV had been considered to occur rarely. However, recent data indicate that sexual transmission of HCV can occur, especially among HIV-infected persons. The Centers for Disease Control and Prevention (CDC) surveillance data demonstrate that 10% of persons with acute HCV infection report contact with a known HCV-infected sex partner as their only risk for infection. Specific studies of HCV transmission between heterosexual or homosexual couples have yielded mixed results, but generally have found low but increased rates of HCV infection in partners of persons with HCV infection compared with those whose partners are not HCV-infected. Several studies have revealed that risk increases commensurate with increasing numbers of sex partners among heterosexual persons and men who have sex with men (MSM), especially if those partners are coinfected with HIV.

Apparent sexual transmission of HCV has recently been reported among HIV-infected MSM in multiple European cities and New York City. Common practices associated with these clusters of infection include serosorting (i.e., HIV-infected men having sex with one another), group sex, and the use of cocaine and other nonintravenous drugs during sex.

All persons with HIV infection should undergo serologic testing for HCV at initial evaluation. HIV-infected MSM can also acquire HCV after initial screening. Liver function tests should be serially monitored for abnormalities that could be caused by acute viral hepatitis or medication toxicity. HIV-infected persons with new and unexplained increases in alanine aminotransferase (ALT) should be tested for acute HCV infection. To ensure the detection of acute HCV infection among HIV-infected MSM with high-risk sexual behaviors or concomitant ulcerative STDs, routine HCV testing of HIV-infected MSM should be considered. Acute hepatitis C is a reportable condition in 49 states, and matching viral hepatitis and HIV surveillance registries can facilitate early detection of social networks of HCV transmission among HIV-infected MSM. Suspected clusters of acute infection should be reported to the appropriate public health authorities. Unprotected sexual contact between HIV-infected partners can facilitate spread of HCV, as the virus can be recovered from the semen of men coinfected with HIV. Specific prevention practices (e.g., barrier precautions that limit contact with body fluids during sexual contact with other MSM) should be discussed with patients.

Diagnosis and Treatment

Anti-HCV testing is recommended for routine screening of asymptomatic persons based on their risk for infection or based on a recognized exposure (see Prevention below). For such persons, testing for HCV infection should include the use of an U. S. Food and Drug Administration (FDA)-cleared test for antibody to HCV (i.e., immunoassay, enzyme immunoassay [EIA], or enhanced chemiluminescence assay and, if recommended, a supplemental antibody test).

Persons counseled and tested for HCV infection and determined to be anti-HCV positive should be evaluated (by referral or consultation, if appropriate) for presence of active infection, presence or development of CLD, and possible treatment. Nucleic acid testing, including reverse transcriptase polymerase chain reaction (RT-PCR) to detect HCV RNA is necessary to confirm the diagnosis of current HCV infection, and an elevated ALT level is biochemical evidence of CLD. Combination therapy with pegylated interferon and ribavirin is the treatment of choice for patients with chronic hepatitis C. Providers should consult with specialists knowledgeable about management of hepatitis C infection because these experts remain cognizant of the latest advances in the field of antiviral therapy for acute and chronic hepatitis C.

Prevention

No vaccine for hepatitis C is available, and prophylaxis with immune globulin is not effective in preventing HCV infection after exposure. Reducing the burden of HCV infection and disease in the United States requires implementation of both primary and secondary prevention activities. Primary prevention reduces or eliminates HCV transmission, whereas secondary prevention activities are aimed at reducing CLD and other chronic diseases in HCV-infected persons by first identifying them and then providing medical management and antiviral therapy, if appropriate.

Most scientific evidence demonstrates that although HCV can be transmitted sexually, such transmission happens rarely. Because incident HCV has not been demonstrated to occur in heterosexual partner-pairs followed over time, condom use might not be necessary in such circumstances. However, heterosexual and homosexual persons, especially those with concurrent HIV infection or with more than one partner, should protect themselves and their partners against transmission of HCV, hepatitis B virus (HBV), HIV, and other pathogens by use of male latex condoms. Condom use is especially important for HIV-infected men, who might spread HCV to other men though unprotected sexual activity.

Providers in STD clinics and other primary-care settings should identify those persons who should be offered HCV counseling and testing. In STD clinics and other settings that serve large numbers of persons at high risk for bloodborne infections (e.g., correctional settings), the major risk factor necessitating screening for HCV infection is past or current injection of illegal drugs. Because both HCV and HIV are transmitted through injection-drug use, about one fourth of all HIV patients are also coinfected with HCV. For this reason, all persons with HIV infection should be offered HCV counseling and testing. Other risk factors for which routine HCV testing is recommended include:

Having had a blood transfusion or solid organ transplant before July 1992

Having received clotting factor concentrates produced before 1987

Having been on long-term dialysis

Having signs and symptoms of liver disease (e.g., abnormal ALT)

Persons who test negative for anti-HCV who had an exposure previously should be reassured that they are not infected. Those who test positive for anti-HCV (see Diagnosis and Treatment above) should be provided information regarding how to protect their liver from further harm; for instance, HCV-positive persons should be advised to avoid drinking alcohol and taking any new medicines (including over-the-counter [OTC] and herbals) without checking with their clinician.

To reduce the risk for transmission to others, HCV-positive persons should be advised to 1) not donate blood, body organs, other tissue, or semen; 2) not share any personal items that might have blood on them (e.g., toothbrushes and razors); and 3) cover cuts and sores on the skin to keep the virus from spreading by blood or secretions. HCV-positive persons with one long-term, steady sex partner do not need to change their sexual practices. They should discuss the low but present risk for transmission with their partner and discuss the need for counseling and testing. HCV-positive women do not need to avoid pregnancy or breastfeeding.

HCV-positive persons should be evaluated (by referral or consultation, if appropriate) to detect active HCV infection and the presence of CLD. Evaluation should involve testing for liver function, additional assessment of the severity of liver disease, possible treatment, and the determination for the need of hepatitis A and B vaccination.

Regardless of test results, persons who use or inject illegal drugs should be counseled to stop using and injecting drugs and to enter and complete substance abuse treatment (including relapse prevention). Persons who continue to inject drugs despite counseling should be encouraged to take the following steps to reduce personal and public health risks:

Never reuse or share syringes, water, or drug preparation equipment

Only use syringes obtained from a reliable source (e.g., pharmacies)

Use a new, sterile syringe to prepare and inject drugs

If possible, use sterile water to prepare drugs; otherwise, use clean water from a reliable source (e.g., fresh tap water)

Use a new or disinfected container (i.e., cooker) and a new filter (i.e., cotton) to prepare drugs

Clean the injection site before injection with a new alcohol swab

Safely dispose of syringes after one use

Get vaccinated for hepatitis A and B if nonimmune; and

Get tested for HIV infection

Postexposure Follow-Up

No postexposure prophylaxis (PEP) has been demonstrated to be effective against HCV. Testing to determine whether HCV infection has developed is recommended for health-care workers after percutaneous or permucosal exposures to HCV-positive blood. Children born to HCV-positive women also should be tested for HCV. Prompt identification of acute infection is important, because outcomes are improved when treatment is initiated earlier in the course of illness.

Special Considerations

Pregnancy

Routine testing for HCV infection is not recommended for all pregnant women. Pregnant women with a known risk factor for HCV infection should be offered counseling and testing. Patients should be advised that approximately six of every 100 infants born to HCV-infected woman become infected; this infection occurs predominantly during or near delivery, and no treatment or delivery method — such as cesarean section — has been demonstrated to decrease this risk. The risk is increased, however, by the presence of maternal HCV viremia at delivery and also is greater (2-3 times) if the woman is coinfected with HIV. HCV has not been shown to be transmitted through breast milk, although HCV-positive mothers should consider abstaining from breastfeeding if their nipples are cracked or bleeding. Infants born to HCV-positive mothers should be tested for HCV infection and, if positive, evaluated for the presence of CLD.

HIV Infection

Because of the high prevalence of HIV/HCV coinfection and because of critical clinical management issues for coinfected persons, all persons with HIV infection should undergo serologic testing for HCV. Providers should be aware of the likelihood that HIV-infected MSM will acquire HCV after initial screening. Liver function tests should be serially monitored, and those persons with new and unexplained increases in ALT should be tested for acute HCV infection. To detect acute HCV infection among HIV-infected MSM with high-risk sexual behaviors or concomitant ulcerative STDs, routine HCV testing of HIV-infected MSM should be considered. Because a small percentage of coinfected persons fail to acquire HCV antibodies, HCV RNA should be tested in HIV-positive persons with unexplained liver disease who are anti-HCV negative. The course of liver disease is more rapid in HIV/HCV coinfected persons, and the risk for cirrhosis is nearly twice that in persons with HCV infection alone. Coinfected persons receiving HIV antiviral regimens are now being treated for HCV after their CD4+ cell counts increase, optimizing their immune response.

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is not specifically stated for each recommendation.

Throughout this guideline document, the evidence used as the basis for specific recommendations is discussed briefly. More comprehensive, annotated discussions of such evidence will appear in background papers that will be published in a supplement issue of the journal Clinical Infectious Diseases.

Benefits/Harms of Implementing the Guideline Recommendations

Qualifying Statements

Qualifying Statements

These recommendations should be regarded as a source of clinical guidance and not prescriptive standards; health-care providers should always consider the clinical circumstances of each person in the context of local disease prevalence. The recommendations are applicable to various patient-care settings, including family planning clinics, private physicians' offices, managed care organizations, and other primary-care facilities. These guidelines focus on the treatment and counseling of individual patients and do not address other community services and interventions that are essential in sexually transmitted disease (STD)/human immunodeficiency virus (HIV) prevention efforts.

Rapporteurs: Hunter Handsfield, MD, University of Washington, Seattle, Washington; William McCormack, MD, State University of New York Health Science Center, Brooklyn, New York; William M. Geisler, MD, University of Alabama, Birmingham, Alabama

Print copies: Available from the Centers for Disease Control and Prevention, MMWR, Atlanta, GA 30333. Additional copies can be purchased from the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402-9325; (202) 783-3238.

Availability of Companion Documents

The following are available:

The Centers for Disease Control and Prevention (CDC) sexually transmitted diseases (STD) treatment guidelines, 2010. eBook for iPad, iPhone, and iPod Touch. Available from the CDC Web site.

2010 STD treatment guidelines webinar: an overview by CDC and the National Network of STD/HIV Prevention Training Centers (NNPTC), including continuing medical education (CME) activity. Available from the CDC Web site. Slides from the webinar are also available from the CDC Web site.

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